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-Structure paper
タイトル | Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F. |
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ジャーナル・号・ページ | Life Sci Alliance, Vol. 3, Issue 11, Year 2020 |
掲載日 | 2020年9月21日 |
著者 | Wout Oosterheert / Katerina T Xenaki / Viviana Neviani / Wouter Pos / Sofia Doulkeridou / Jip Manshande / Nicholas M Pearce / Loes Mj Kroon-Batenburg / Martin Lutz / Paul Mp van Bergen En Henegouwen / Piet Gros / |
PubMed 要旨 | Tetraspanins are eukaryotic membrane proteins that contribute to a variety of signaling processes by organizing partner-receptor molecules in the plasma membrane. How tetraspanins bind and cluster ...Tetraspanins are eukaryotic membrane proteins that contribute to a variety of signaling processes by organizing partner-receptor molecules in the plasma membrane. How tetraspanins bind and cluster partner receptors into tetraspanin-enriched microdomains is unknown. Here, we present crystal structures of the large extracellular loop of CD9 bound to nanobodies 4C8 and 4E8 and, the cryo-EM structure of 4C8-bound CD9 in complex with its partner EWI-F. CD9-EWI-F displays a tetrameric arrangement with two central EWI-F molecules, dimerized through their ectodomains, and two CD9 molecules, one bound to each EWI-F transmembrane helix through CD9-helices h3 and h4. In the crystal structures, nanobodies 4C8 and 4E8 bind CD9 at loops C and D, which is in agreement with the 4C8 conformation in the CD9-EWI-F complex. The complex varies from nearly twofold symmetric (with the two CD9 copies nearly anti-parallel) to ca. 50° bent arrangements. This flexible arrangement of CD9-EWI-F with potential CD9 homo-dimerization at either end provides a "concatenation model" for forming short linear or circular assemblies, which may explain the occurrence of tetraspanin-enriched microdomains. |
リンク | Life Sci Alliance / PubMed:32958604 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.33 - 8.6 Å |
構造データ | EMDB-11053: PDB-6rlr: PDB-6z1v: PDB-6z1z: PDB-6z20: |
化合物 | ChemComp-HOH: ChemComp-PGE: ChemComp-EDO: ChemComp-ACY: ChemComp-GOL: ChemComp-CL: |
由来 |
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キーワード | IMMUNE SYSTEM / CD9 antigen / tetraspanin / CELL ADHESION / Antibody-antigen complex / EC2 domain / nanobody / CD9-binding / CD9 |